System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Clinical Trial, Phase I Clinical Trial, Phase II Randomized Controlled Trial Multicenter Study Ppublish 1 citation

PubMed: 42189888 DOI: 10.1158/1078-0432.CCR-25-4417

Durvalumab plus Paclitaxel, with or without Capivasertib or Oleclumab, in Patients with Locally Advanced/Metastatic Triple-Negative Breast Cancer.

Clin Cancer Res 32(16):3506-3516

Authors: Peter Schmid, Cynthia X Ma, Yeon Hee Park, Simon Lord, Anne Armstrong, Seock-Ah Im, Shin-Cheh Chen, Ricardo Fernandes, Jacek Jassem, Piotr J Wysocki, Yen-Shen Lu, Hwei-Chung Wang, Wei-Pang Chung, Purnima Rao-Melacini, Katrin Heider, Ross Stewart, Petra Vuković, Kyung Hae Jung

Affiliations

  • Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
  • Washington University School of Medicine, St. Louis, Missouri.
  • Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
  • Medical Sciences Division, University of Oxford, Oxford, United Kingdom.
  • Christie Hospital NHS Foundation Trust and Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
  • Seoul National University Hospital , Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea.
  • Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
  • Schulich School of Medicine & Dentistry, Western University, London Health Sciences Centre, London, Canada.
  • Medical University of Gdańsk , Gdańsk, Poland.
  • Jagiellonian University - Medical College, Krakow, Poland.
  • National Taiwan University Hospital , Taipei, Taiwan.
  • Surgical Department, China Medical University Hospital, Taichung, Taiwan.
  • National Cheng Kung University Hospital , College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • Late Phase Oncology, AstraZeneca, Mississauga, Canada.
  • Late Phase Oncology, AstraZeneca, Cambridge, United Kingdom.
  • Translational Medicine Oncology, AstraZeneca, Cambridge, United Kingdom.
  • Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea.

Abstract

PURPOSE

Triple-negative breast cancer (TNBC) is a heterogeneous disease with high recurrence rates and poor prognosis, often requiring multiple therapies. BEGONIA was a phase Ib/II, multiarm, platform study evaluating the safety and efficacy of first-line treatment combinations with durvalumab (anti-PD-L1 antibody) for locally advanced, unresectable/metastatic TNBC (mTNBC; NCT03742102). In this study, we report results of 3 treatment arms.

PATIENTS AND METHODS

Eligible female participants (≥18 years with untreated, unresectable, locally advanced/mTNBC) received durvalumab plus paclitaxel or were randomized to this treatment in combination with capivasertib (pan-AKT inhibitor) or oleclumab (anti-CD73 antibody). The primary objective was safety and tolerability; secondary endpoints included objective response rate (ORR).

RESULTS

Twenty-three patients received durvalumab plus paclitaxel, 31 received capivasertib combination, and 33 received oleclumab combination. Maximum grade 3/4 adverse events occurred in 10 of 23 (43.5%), 25 of 31 (80.6%), and 8 of 33 (24.2%) patients in the durvalumab plus paclitaxel, capivasertib-combination, and oleclumab-combination arms, respectively. The confirmed ORR (95% confidence interval) was 56.5% (34.5-76.8) with durvalumab plus paclitaxel, 54.8% (36-72.7) with capivasertib combination, and 51.5% (33.5-69.2) with oleclumab combination. Responses were observed across biomarker subgroups, including PD-L1, PIK3CA/AKT1/PTEN alterations, and CD73, with a trend for improved activity in the PD-L1-positive subgroups.

CONCLUSIONS

These findings support the clinical activity and tolerability of durvalumab plus paclitaxel in locally advanced unresectable/mTNBC, as expected for an immune checkpoint inhibitor in combination with chemotherapy. The addition of capivasertib or oleclumab to this treatment combination showed no substantial additional benefit. PD-L1 expression was associated with enhanced antitumor activity across all arms.

MeSH

Triple Negative Breast Neoplasms, Safety, Breast Neoplasms, Paclitaxel, Neoplasms, Breast, Therapeutics